Membranous And Cytoplasncy Catenin Case Study

If the APC protein were to experience a nonsense mutation, the most common mutation in regards to this specific genetic disease, the destruction complex would not perform correctly and the wnt-signaling pathway would be stimulated. Problems begin to arise when “the Wnt/Beta-catenin pathway is activated [by] a Wnt ligand [binding] to seven-pass transmembrane Frizzled receptor and its co-receptor, low-density lipoprotein related protein 6 (LRP6) or its close relative LRP5” (MacDonald, et. al 2009). Once the wnt-signaling pathway is stimulated, a Wnt-Fz-LRP6 complex forms and takes in the Dishevelled (Dvl) protein, resulting in the phosphorylation and activation of the recruitment of the axin complex, destruction complex, to the receptors. (MacDonald, et al 2009). Due to the phosphorylation within the Wnt-Fz-LRP6 complex, the axin complex is not able to phosphorylate Beta-Catenin, which leads to the excessive accumulation of the protein in the cytoplasm. Researchers witnessed the development of numerous intestinal adenomas in transgenic mice with stabilized mutant Beta-catenin, therefore the results suggest that dysregulation of Beta-catenin is a key oncogenic event that follows the loss of APC function. (Tarapore, et. al 2011). The loss of the destruction complex’s normal activities results in elevated levels of Beta-catenin and downstream effectors such as CCND1,

Immunoblot analysis showed that GSK-3β knockdown caused significantly enhanced the level of β-catenin that activate the Wnt pathway, while BPA treatment decreased the level of β-catenin that enhanced due to GSK-3β knockdown group (Figure 10G-H). Furthermore, the level of downstream target genes of Wnt/β-catenin pathway such as cyclinD1 and survivin after GSK-3β knockdown enhanced but BPA treatment caused decreased their levels that enhanced due to GSK-3β knockdown (Figure

All epithelial tissues have cytokeratin in them and potentially malignant disorders like OSF have epithelial component.Cytokeratin that form the cytoskeletons of the epithelial cells are of several molecular types. The patterns of expression of these different types of CKs vary depending upon the type of epithelial cells and hence, they may be used as potential markers of cell differentiation and malignant transformation. CK 19, a type I (acidic) keratin, is the smallest keratin and is unique in that it lacks the Carboxyterminal, non ‑ α ‑ helical tail domain, which is typical for all other keratins10.

Catenins play a crucial role in cadherin function. E cadherins and catenins are proteins that are involved in intercellular adhesion. It has been suggested that lack of alpha, beta or gamma catenins enable tumor progression. Immunohistochemical analysis of intracellular beta-catenin and WNT-1 levels in basal cell carcinoma had

It also has been shown that cyclin D1 is a downstream target of the β-catenin–TCF complex and therefore when continually activated allows cells to proceed through cell cycle and continue tumor growth. In support of this, expression of the dominant-negative form of TCF, lacking the β-catenin binding domain, in colon-cancer cells strongly inhibits expression of cyclin D1 causing cells to arrest in the G1 phase of the cell cycle due to the lack of activation of cyclin D1 [23]).

In the present study, we demonstrate the stimulatory roles of COX-2 and EP4 in human breast cancer progression and SLC induction via PI3K/AKT/NOTCH and WNT pathways, combining in vitro, in vivo, and in situ approaches. This work supports our previous studies, wherein we showed SLC stimulatory roles of COX-2 and EP4 in a murine breast cancer model [5]. The role of COX-2 in SLC induction has been hypothesized [42] and the roles of EP4 documented in human breast cancer cells [43]. We reported that COX-2/EP4 mediated induction of an oncogenic microRNA-526b was linked with SLC stimulation [19]. However, the mechanisms underlying COX-2/EP4 mediated SLC induction in human breast cancer remained unclear. In the present study, for the first time,

Lee et al cultured two strains of OSCC cells, SAS cells treated by AG1478 (inhibitor of EGFR) and OECM1 cells treated with EGF (activator of EGFR). While the SAS cells showed decrease in nuclear β catenin with increase in membranous β catenin, OECM1 cells showed increased amount of nuclear β catenin overtime. This showed that EGFR plays a vital role in Wnt signalling influencing the stabilisation and nuclear accumulation of β catenin. They also showed that histone markers effect the expression on target gene, cyclin D1. These ultimately lead to the progression of oral cancer. (Lee et al, 2010). c‑myc was among the first oncogenes found to be amplified in breast cancer, and it can contribute to many other forms of cancer

Since its discovery as a product of the alternate reading frame of the mouse Arf/Ink4a locus signals, the Arf tumor suppressor has been identified as a key sensor of hyperproliferative stimuli such as those originating from mutant Ras and c-Myc oncoproteins to prevent early stage cancer cells to undergo neoplastic transformation by inducing senescence or apoptosis (reviewed in Refs. 1, 2). p19Arf and p16Ink4a are transcribed from separate and unique first exons 1β and 1α (18 kilo base pairs [kb] apart in mice and 23kb in humans) which splice into two shared exons 2 and 3 (Fig. 1). These two genes are different tumor suppressor since p19Arf uses only exons 1 and 2 while p16Ink4a uses all of the exons 1-3 for production of

P53 tumor suppressor plays a vital role in the prevention of transformation of oncogene. However, stresses from area such as DNA damage, oncogenes, spindle damages etc. can cause a mutation in TP53 tumor suppressor gene which can alter and cause disturbance in the P53 pathway which involved certain protein and genes regulator dealing with growth arrest, apoptosis, DNA repair and angiogenesis.

To identify the actual proteins responsible for the tongue cancer chemopreventive activity of Streblus asper extracts, especially the ERK ½, caspases, and Bcl-2 family together with the proteins related to the cells proliferative activity such as Ki-67, PCNA, cyclin D1, p21 and p27 as well as the signal transduction pathway such as Mitogen-activated protein kinases (MAPKs) pathway.

Bryne M. (1998) suggested that molecular and morphological characteristics at the invasive front area of various squamous cell carcinomas may reflect tumor prognosis better than other parts of the tumor. Several molecular events are important for tumor spread like gains and losses of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumor host interface; consequently they have developed a simple morphological malignancy grading system

miRNA’s have been found in many organisms even including plants. They have been shown to regulate various processes , some as fundamental as development, and differentiation. Their role has been found to be a negative regulator of gene expression. miRNA’s bind to the transcribed mRNA and cause it to be degraded, thus inhibiting the production of the gene product. It is not surprising that in cancer, miRNAs could either inappropriately repress anti-tumor mechanisms (such as steps in the apoptosis pathways) or loss of the miRNA

JAK2/STAT signaling pathway was one of most significantly differentially expressed gene sets in BC compared with CP progenitors. This signaling pathway increases the ADAR1 expression in progenitor LSCs and promotes ADAR1-mediated A-to-I editing. Furthermore, ADAR1 impairs biogenesis of tumour suppressive miRNAs, thereby contributing to cancer progression. Since the let-7 miRNA family is also related to self renewal of LSC, it led the authors to investigate the correlation between JAK2/STAT pathway and LIN28B/let-7-axis, they hypothesized that the LIN28B/let-7self-renewal axis may also be disrupted by increased JAK2 signaling. This hypothesis was validated by a lentiviral transduction of BCR-ABL1 in normal progenitor, it shows an increase

The aim of this study is to investigate the role of canonical Wnt signalling pathway in tumorigenesis of oral squamous cell carcinoma of south Indian origin.

My project work is focused on understanding the role of non-coding RNA – miRNAs regulating cellular proliferation during oncogenic transformations. miRNA targeting mRNA regulates gene expression post transcriptionally and plays an important role in tumor progression. To identify differentially expressed miRNAs in Osteosarcoma cell lines which have different proliferation rates, I have screened miRNAs from relevant microRNA datasets and upregulated and downregulated microRNAs were shortlisted and their expression were analyzed in the respective OS cell line by real-time RT PCR. Potential targets for miRNAs were screened for cell cycle and DNA replication genes by target scan and KEGG database. Downregulated miRNAs were overexpressed in OS cell lines by transfecting the synthetic mimics/ inhibitors and checked the expression levels of the target protein at RNA level by qRT PCR and at protein level by Immunoblotting. Further cell